Hepatocellular CarcinomaPhase 1/2NCT00946153
Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)
A Phase 1/2 study testing Lenvatinib in people with Hepatocellular Carcinoma, run by Eisai Co., Ltd. at 12 sites in 2 countries.
Trial summary
The purpose of this study is to determine maximum tolerated dose (MTD), efficacy, safety and tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor effect of E7080 when is administered continually once daily in participants with advanced hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 24 Jul 2009to 13 Aug 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or clinically confirmed diagnosis of advanced HCC.
- Eastern Cooperative Oncology Group-Performance Status (ECOG-PS): 0-1.
- Adequate laboratory values/organ function tests.
Who cannot join
- Simultaneous or metachronous cancers.
- Pericardial, ascites, or pleural effusion requiring drainage.
- Brain metastasis/meningeal carcinomatosis presenting clinical symptoms or requiring treatment.
- Malabsorption syndrome.
- Artery-portal vein shunt or artery-vein shunt preventing proper diagnosis of tumor.
- Use of drugs known to inhibit cytochrome P3A4.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Japan10 sites
Study site
Chuo-ku, Tokyo
Study site
Kashiwa-shi, Chiba
Study site
Kawasaki-shi, Kanagawa
Study site
Kurume-shi, Fukuoka
Study site
Minato-ku, Tokyo
Study site
Musashino-shi, Tokyo
Study site
Osaka, Osaka
Study site
Osakasayama-shi, Osaka
Study site
Saga, Saga-ken
Study site
Sapporo, Hokkaido
South Korea2 sites
Study site
Gangnam-gu, Seoul
Study site
Songpa-gu, Seoul
About this study
Official title: Phase I/II Study of E7080 in Patients With Advanced Hepatocellular Carcinoma (HCC)
The purpose of this study is to determine maximum tolerated dose (MTD), efficacy, safety and tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor effect of E7080 when is administered continually once daily in participants with advanced hepatocellular carcinoma.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Lenvatinib
- Keywords
- Carcinoma, Hepatocellular
- Medical subject headings
- Carcinoma, Hepatocellular, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080
In the Dose-Escalation Component of the study, lenvatinib will be administered as continuous once-daily oral dosing. Dose-escalation will occur based on safety information obtained during Cycle 1. The recommended dose for the Expansion Component of the study will use the MTD in Cycle 1.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib | Experimental | Not described Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib
The MTD was defined as the highest dose level at which no more than 1 of 6 participants had a dose limiting toxicities (DLT). DLT was defined as any of the following events: grade 4 or higher hematologic toxicity or grade 3 thrombocytopenia that required blood transfusion, grade 3 or higher nonhematologic toxicity, grade 4 hypertension uncontrolled by antihypertensive drug(s), aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than (>) 10.0*upper limit of normal (ULN), proteinuria 4+ by urine dipstick, proteinuria 3+ by urine dipstick was to be monitored by 24-hour urine collection, proteinuria >3.5 gram (g) for 24 hours, diarrhea/vomiting/nausea of grade 3 or higher that was uncontrollable despite maximal supportive therapies and abnormal clinical laboratory values that required no treatment, grade 3 proteinuria by dipstick, diarrhea/vomiting/nausea that was managed with supportive therapies were not considered as DLT.
Measured: Up to 28 days (Cycle1)
Phase 2: Time to Progression (TTP) by Independent Review Assessment
TTP was defined as the time from the date of registration to the date when progressive disease (PD) was first confirmed. PD was evaluated according to modified response evaluation criteria in solid tumors (mRECIST) by an independent imaging review. PD was defined as at least a 20 percent (%) increase in the sum of long diameter (LD) of target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 millimeter (mm) (including new lesions).
Measured: From day of registration to the day when PD was first confirmed (approximately up to 6.1 years)
Secondary outcomes (7)
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
BOR was performed using RECIST1.1 and was measured as complete response (CR) defined as when an overall response of CR was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of CR was confirmed and the BOR established as CR was regarded as the "CR confirmed date), partial response (PR) defined as when the overall response of PR or better (CR or PR) was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of PR was confirmed and the BOR established as PR will be regarded as the "PR confirmed date), PD defined as when the BOR was neither CR, PR, or stable disease (SD), and the overall response was PD, SD defined as when the BOR obtained was neither CR nor PR, but no PD from the initial administration to the end of Cycle 2 and the overall response of SD or better occurred at least once and not evaluable (NE) was when the overall response was NE in all cases.
Measured: Every 8 weeks (approximately up to 18.4 months)
Phase 1: Objective Response Rate (ORR) by Investigator Assessment
ORR was defined as the percentage of participants who achieved a tumor response measured by RECIST 1.1 of CR defined as disappearance of all target lesions (a short diameter is less than (<)10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Measured: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Phase 1: Disease Control Rate (DCR) by Investigator Assessment
DCR was measured by RECIST 1.1 and defined as CR which was defined as disappearance of all target lesions (a short diameter was <10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.
Measured: Up to Week 16
Phase 2: Progression-free Survival (PFS) by Independent Review Assessment
PFS was defined as the time from the date of registration until the date when PD was first confirmed or death (whichever occurred first) as determined by mRECIST and PD was defined as at least a 20% increase in the sum of long diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Measured: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Phase 2: Objective Response Rate (ORR) by Independent Review Assessment
ORR was defined as the percentage of participants who achieved a tumor response measured by mRECIST of CR defined as disappearance of all target lesions (a short diameter is <10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Measured: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
DCR was measured by mRECIST and defined as CR which was defined as disappearance of all target lesions (a short diameter is <10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.
Measured: Weeks 8 and 16
Phase 2: Overall Survival (OS)
OS was defined as the time from the date of registration until the date of death.
Measured: From day of registration to the day of death (approximately 6.1 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2009 (estimated)
- Study start24 Jul 2009
- Primary completion15 Jun 2014
- Study completion13 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00946153
- Sponsor's protocol ID
- E7080-J081-202
- Status last verified
- Jul 2018
- First submitted
- 23 Jul 2009
- Last updated
- 1 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Ikeda K, Kudo M, Kawazoe S, Osaki Y, Ikeda M, Okusaka T, Tamai T, Suzuki T, Hisai T, Hayato S, Okita K, Kumada H. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2017 Apr;52(4):512-519. doi: 10.1007/s00535-016-1263-4. Epub 2016 Oct 4.
PubMed 27704266
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of E7080 in Patients With Advanced Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT00946153
- Acronym / sponsor ID
- E7080-J081-202
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Carcinoma, Hepatocellular
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Eisai Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 24 Jul 2009 (actual)
- Primary completion
- 15 Jun 2014 (actual)
- Study completion
- 13 Aug 2015 (actual)
- First posted
- 24 Jul 2009 (estimated)
- Results
- Posted 1 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine maximum tolerated dose (MTD), efficacy, safety and tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor effect of E7080 when is administered continually once daily in participants with advanced hepatocellular carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib | Experimental | Drug: Lenvatinib |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Histologically or clinically confirmed diagnosis of advanced HCC.
- Eastern Cooperative Oncology Group-Performance Status (ECOG-PS): 0-1.
- Adequate laboratory values/organ function tests.
Key exclusion criteria (6 listed)
- Simultaneous or metachronous cancers.
- Pericardial, ascites, or pleural effusion requiring drainage.
- Brain metastasis/meningeal carcinomatosis presenting clinical symptoms or requiring treatment.
- Malabsorption syndrome.
- Artery-portal vein shunt or artery-vein shunt preventing proper diagnosis of tumor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E7080In the Dose-Escalation Component of the study, lenvatinib will be administered as continuous once-daily oral dosing. Dose-escalation will occur based on safety information obtained during Cycle 1. The recommended dose for the Expansion Component of the study will use the MTD in Cycle 1. | Drug | Lenvatinib |
Primary outcome
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib
Time frame: Up to 28 days (Cycle1)
The MTD was defined as the highest dose level at which no more than 1 of 6 participants had a dose limiting toxicities (DLT). DLT was defined as any of the following events: grade 4 or higher hematologic toxicity or grade 3 thrombocytopenia that required blood transfusion, grade 3 or higher nonhematologic toxicity, grade 4 hypertension uncontrolled by antihypertensive drug(s), aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than (>) 10.0*upper limit of normal (ULN), proteinuria 4+ by urine dipstick, proteinuria 3+ by urine dipstick was to be monitored by 24-hour urine collection, proteinuria >3.5 gram (g) for 24 hours, diarrhea/vomiting/nausea of grade 3 or higher that was uncontrollable despite maximal supportive therapies and abnormal clinical laboratory values that required no treatment, grade 3 proteinuria by dipstick, diarrhea/vomiting/nausea that was managed with supportive therapies were not considered as DLT.
Phase 2: Time to Progression (TTP) by Independent Review Assessment
Time frame: From day of registration to the day when PD was first confirmed (approximately up to 6.1 years)
TTP was defined as the time from the date of registration to the date when progressive disease (PD) was first confirmed. PD was evaluated according to modified response evaluation criteria in solid tumors (mRECIST) by an independent imaging review. PD was defined as at least a 20 percent (%) increase in the sum of long diameter (LD) of target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 millimeter (mm) (including new lesions).
7 secondary outcomes
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Time frame: Every 8 weeks (approximately up to 18.4 months)
Phase 1: Objective Response Rate (ORR) by Investigator Assessment
Time frame: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Phase 1: Disease Control Rate (DCR) by Investigator Assessment
Time frame: Up to Week 16
Phase 2: Progression-free Survival (PFS) by Independent Review Assessment
Time frame: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Phase 2: Objective Response Rate (ORR) by Independent Review Assessment
Time frame: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
Time frame: Weeks 8 and 16
Phase 2: Overall Survival (OS)
Time frame: From day of registration to the day of death (approximately 6.1 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27704266Ikeda K, Kudo M, Kawazoe S, Osaki Y, Ikeda M, Okusaka T, Tamai T, Suzuki T, Hisai T, Hayato S, Okita K, Kumada H. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2017 Apr;52(4):512-519. doi: 10.1007/s00535-016-1263-4. Epub 2016 Oct 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenvatinib in people with Hepatocellular Carcinoma, run by Eisai Co., Ltd. at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Japan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib (time frame: Up to 28 days (Cycle1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00946153, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.